Jeppsson A, Höltta Mikko, Zetterberg H, Blennow K, Wikkelsø C, Tullberg Mats
Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Fluids Barriers CNS. 2016 Jul 29;13(1):13. doi: 10.1186/s12987-016-0037-y.
Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) and α- and β-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPβ). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery.
Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), Aβ isoforms Aβ38, Aβ40 and Aβ42, sAPPα, sAPPβ, APLP1 β-derived peptides APL1β25, APL1β 27 and APL1β 28 and YKL40 by immunochemical methods.
The concentrations of all soluble forms of APP, all Aβ isoforms and APL1β28 were lower, whilst APL1β25 and APL1β27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged.
The reduced CSF concentrations of Aβ38, Aβ40, Aβ42, sAPPα and sAPPβ suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1β25 and APL1β27 in combination with a slight decreased APL1β28 could be caused by more available γ-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.
特发性正常压力脑积水（iNPH）患者脑脊液（CSF）中淀粉样蛋白β（Aβ）以及淀粉样前体蛋白的α和β裂解可溶性形式（sAPPα和sAPPβ）的浓度降低。本研究的目的是检查APP样蛋白1（APLP1）的分泌代谢产物在CSF中是否也会出现变化，并探讨淀粉样蛋白相关CSF生物标志物以及神经元损伤和星形胶质细胞活化标志物对分流手术后临床结局的预后价值。
纳入20例诊断为iNPH的患者，其中10例经分流手术病情改善，10例未改善，以及20名神经功能正常的对照者。所有患者在手术前和手术后6个月随访时使用iNPH量表进行临床检查。术前进行腰椎穿刺。通过免疫化学方法分析CSF样本中的神经丝轻链（NFL）、Aβ亚型Aβ38、Aβ40和Aβ42、sAPPα、sAPPβ、APLP1β衍生肽APL1β25、APL1β27和APL1β28以及YKL40。
与对照组相比，iNPH患者CSF中所有APP可溶性形式、所有Aβ亚型和APL1β28的浓度较低，而APL1β25和APL1β27的浓度较高。手术后病情改善的患者和未改善的患者之间生物标志物浓度没有差异。
CSF中Aβ38、Aβ40、Aβ42、sAPPα和sAPPβ浓度降低表明iNPH中APP表达可能下调。相比之下，CSF中APLP1浓度似乎相对未变。APL1β25和APL1β27的增加以及APL1β28的轻微降低可能是由于其主要底物APP的可用性降低导致γ-分泌酶可用性增加所致。数据不支持将这些标志物用作分流反应性的指标。
